Although the coordination of growth and differentiation is fundamental to the development of all metazoans, little is known about how developmental signals are communicated to the cell cycle machinery. The unit on cell cycle regulation uses Drosophila oogenesis as a model system to examine the developmental regulation of the cell cycle. Our current research is focused on two problems: The regulation of the endo cycle and the relationship between cell cycle regulation and oocyte differentiation. During Drosophila oogenesis both germ-line derived nurse cells and somatic follicle cells enter the endo cycle and become polyploid. In the endo cycle, cells undergo successive rounds of DNA replication without an intervening mitosis. One goal of the laboratory is to understand how cells enter and maintain the endo cycle in response to specific developmental cues. Towards this end, we have designed a genetic screen, based on the FLP/FRT site specific recombinase system, to identify and characterize genes that regulate the endo cycle. This screen provides a general tool for the genetic dissection of pathways that control cell cycle regulation in the ovary. We are currently characterizing several mutants identified in a large scale FLP/FRT screen. In addition to our studies of the endo cycle, we are examining how cell cycle regulation influences cellular differentiation during oogenesis. In Drosophila a single oocyte develops within a 16-cell germ-line cyst. Throughout much of oogenesis, as is observed in most metazoans, the oocyte remains arrested in prophase of meiosis I. In contrast, its 15 mitotic sisters enter the endo cycle and become polyploid in preparation for their role as nutritive nurse cells. We have demonstrated that the differential regulation of the p21CIP/p27Kip like CycE-Cdk2 inhibitor Dacapo is critical to the maintenance of these two independent modes of cell cycle regulation within germ-line cysts and ultimately to the differentiation of both the nurse cells and oocyte. We are continuing to examine how CycE-Cdk2 activity is spatially and temporally regulated during germ-line cyst formation and maturation. Finally, mutations in the twin gene alter both oocyte differentiation and cell cycle regulation in ovarian germ-line cysts. Our phenotypic analysis of twin mutants indicates that characterization of the twin gene may further our understanding of both cell cycle control and cell fate decisions in the germ line. We have undertaken a detailed molecular and genetic characterization of the twin locus.